System for providing biological materials

ABSTRACT

System and process for isolating purified biological materials with a collecting unit which has collecting vessels that are accessible from above with a matrix unit in which matrix vessels are arranged in a holder as well as a closure unit which can be placed on the collecting unit to close the collecting vessel. In addition the invention also concerns a system having a collecting unit, a matrix unit, and a closure unit as well as a lysis unit and a waste unit. Moreover a new closure arrangement is disclosed which is suitable for closing vessels in which there is excess pressure.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority under 35 U.S.C. §119 of GermanApplication Serial No. 197 34 135.7 filed Aug. 7, 1997.

FIELD OF THE INVENTION

The present invention concerns a system which enables the user toprocess biological samples by contacting the sample with a matrix whichbinds the desired biological materials and subsequently eluting thebiological materials from the matrix. This method of isolatingbiological materials is used especially in the field of cell analysis ornucleic acid analyses where relatively small amounts of biologicalmaterials are required.

BACKGROUND AND SUMMARY OF THE INVENTION

Devices are already known in the prior art which use matrices to bindand purify nucleic acids. For example a vessel is described in EP-A-0738 733 into which a liquid sample can be added which has a porousmatrix on its underside to which nucleic acids can be bound by drawingthe sample through the matrix. In addition a device is described inDE-4143394 which has a plurality of vessels arranged next to one anotherwhich have a layer of selectively adsorbing material at the bottom andan outlet opening on the underside of the vessels. The describedarrangement of vessels is placed on a unit of sample holding vesselssuch that liquid from the former vessels pass into the collectingvessels after passage through the layer of adsorbing material.Furthermore the so-called QUIamp kit is known from the Quiagen Companywhose function is shown in FIG. 1. Firstly a sample liquid together witha lysis buffer is added to a sealable vessel and a lysis of the mixtureis carried out. In the subsequent step the lysis mixture is added to avessel containing a matrix capable of specific binding and is drawnthrough the matrix by centrifugation and the emerging liquid iscollected in a vessel. The matrix is subsequently washed and finally theadsorbed biological material is eluted.

A disadvantage of the prior art is that the user who is usuallyconfronted with a large number of different samples has little supportin automating his processes. In the system of the prior art shown inFIG. 1 individual vessels are used to process the sample so that whenseveral samples are processed in parallel individual vessels are alwayspresent which can easily be mixed up. In contrast labelling each vesselmeans some work for the operator so that it is often not done. Mixing upsamples can have disastrous consequences especially when processingnucleic acids which is frequently used to detect diseases or forcriminal investigations.

There is still no known concept in the prior art which would suitablyassist a user with a large number of samples either by accelerating themanual processing or automating the processing.

Hence an object of the present invention was to propose a system forproviding biological materials which enables a coordinated, simpleprocessing of a plurality of sample materials which prevents mistakesand contamination. A further object of the present invention was toprovide a system and process which can adequately exclude thepossibility of mistaking samples. A further aspect of the presentinvention relates to the problem of providing a closure design whichtakes into account the specific requirements needed to providebiological materials.

The above objects are achieved by a process for isolating a purifiedbiological material comprising the following steps:

a) Placing biological materials in separate lysis vessels of a lysisunit comprising two or several lysis vessels in a predeterminedgeometric arrangement,

b) adding lysis liquids to the biological materials in the lysisvessels,

c) transferring the liquids in the lysis vessels into a matrix unitcontaining matrix vessels with outlet openings whose number correspondsto the number of lysis vessels which are arranged in a predeterminedgeometric arrangement and a matrix is located in each of the matrixvessels to which the biological material to be purified binds,

d) extracting the liquids in the matrix vessels through the outletopenings during which the liquids flow through the matrices,

e) placing the matrix unit on a collecting unit with collecting vesselswhich are arranged such that at least the outlet openings of the matrixvessels extend into the collecting vessels,

f) filling the matrix vessels with elution fluid,

g) extracting the elution fluids from the matrix vessels through theiroutlet openings during which the elution fluids flow through thematrices and the elution fluids which are enriched with biologicalmaterial are collected in the collecting vessels.

The process mentioned above for obtaining purified biological materialshas the advantage over the prior art that it enables the processingsteps to be systematized due to the predetermined geometric arrangementsof the lysis unit, matrix unit and collecting unit. The predeterminedgeometric arrangement of the lysis vessels which preferably correspondsto the geometric arrangement of the matrix vessels in the matrix unitmakes it easier for the user to transfer a lysed biological materialfrom a collecting vessel into the corresponding matrix vessel.Furthermore the arrangement of matrix vessels corresponds to that of thecollecting vessels in such a manner that at least the outlet openings ofthe matrix vessels extend into the collecting vessels when the matrixunit is placed on the collecting unit.

The assembly of lysis vessels, matrix vessels and collecting vesselswhich forms the corresponding units has the additional advantage that itis not necessary to handle individual vessels but rather whole units canbe moved whose size and shape are much easier to handle.

In the said process it is additionally possible to use codes on theindividual units which enable a sample placed in a lysis vessel to beunambiguously assigned to the eluate that is finally collected.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a diagrammatic view of a so-called QUIamp kit;

FIG. 2 is a diagrammatic view of the process of the present invention;

FIG. 3a shows a lysis unit in a perspective view;

FIG. 3b shows a cross-section through FIG. 3a along the line A-A′;

FIG. 4a shows a matrix unit, which has two rows of eight matrix vessels;

FIG. 4b is a cross-section through FIG. 4a along the line B-B′;

FIG. 5 shows a perspective view of a waste unit;

FIG. 6 shows a perspective view of a collecting unit;

FIG. 7 shows a cross-section through an arrangement of matrix unit andcollecting unit;

FIG. 8a shows in a perspective view that the collecting unit can beclosed with the closure unit;

FIG. 8b shows an arrangement of the closure unit and the collectingunit;

FIG. 9a shows the cap in the opened position; and

FIG. 9b shows the cap in the closed position.

DETAILED DESCRIPTION OF THE INVENTION

The above-mentioned process is further elucidated by FIG. 2.

FIG. 2 shows a sample (1) which is placed in a lysis vessel (11) of thelysis unit (10) using a pipette (2). A lysis liquid is also added to thesame lysis vessel (11). The other lysis vessels of the lysis unit (10)can be filled with other sample liquids and with the same or other lysisliquids. The lysis unit (10) has closures (12) that are used to closethe lysis vessels and whose number corresponds to the number of lysisvessels. Preferably only the respective lysis vessel to which the liquidis added is opened during the pipetting steps to exclude contaminationof the other lysis vessels for example by falling drops. Theconstruction of the lysis unit is elucidated later in more detail byFIGS. 3A and 3B. At this point only the sample and reagents as well asthe process steps are described in detail.

Sample materials which can be processed with the present invention arefor example liquids such as blood, saliva etc.; it is however, alsopossible to use solid samples such as e.g. pieces of tissue etc.

Lysis liquids are known in the prior art and they are usually alkalinesolutions of alkyl sulphates or other compounds that damage the cellwalls. Cell walls of cells contained in the sample are destroyed duringlysis to release the cell contents and in particular nucleic acids. Forthis the mixture of sample and lysis liquid is usually incubated for aperiod of a few minutes at an elevated temperature such as 70° C. Themixture obtained is referred to as the lysis mixture in the following.

FIG. 2 also shows a combination of a matrix unit (20) and a waste unit(30). After the sample has been lysed in the lysis unit (10), the lysismixture is pipetted from a lysis vessel into a matrix vessel (21) of thematrix unit (20). The pipetting from the lysis unit into the matrix unitis preferably carried out such that the pipetting takes place betweencorresponding vessels i.e. a pipetting is carried out from vessel 1 ofthe lysis unit into vessel 1 of the matrix unit. For this purpose thelysis and matrix unit are preferably provided with numbers, letters orsuch like that enable corresponding vessels to be put in order. Theaforementioned pipetting step is also preferably carried out such thatonly the cap (22) of the vessel into which the liquid is to be pipettedis opened. This also avoids a contamination of the other matrix units.The waste unit (30) with cavities into which the liquid emerging fromthe matrix vessels is collected is located below the matrix unit. Thematrix unit (20) is placed on the waste unit (30) in such a manner sothat each of the matrix vessels extends into a corresponding cavity ofthe waste unit. This prevents mixing of liquids emerging from differentmatrix vessels. This could be tolerated if it could be ensured by anadequate depth of the construction and appropriate procedures that thematrix vessels do not come into contact with the liquid mixture and thatthe matrix is not contaminated with foreign sample materials. However,in order to maintain a small depth of the construction and to avoidcontamination of the matrix vessels, an individual cavity is preferablyprovided for each of the matrix vessels. In addition it is advantageousto cover the cavities with an absorbent material for example a fleecewhich absorbs the waste liquids so that no movement of liquid occursduring transport that could lead to contamination of the matrix.

The added lysis mixture can for example be removed from the matrixvessels —(21)— by applying negative pressure to the cavities —(35)— ofthe waste unit —(30)— or by applying positive pressure to the inletopenings —(27)— of the matrix vessels —(21)—. However, the system shownin FIG. 2 is designed such that the lysis mixture can be removed in asimple manner from the—outlet openings (28) of —matrix vessels —(21)— bycentrifugation. For this the arrangement of matrix unit —(20)— and wasteunit —(30)— filled with lysis liquids is placed in a centrifuge and thefluids are moved through the matrices —(29)— by centrifugal force. Thesize of the arrangement is preferably such that it can be used incentrifuges suitable for microtitre plates. As the liquids pass throughthe matrices —(29)— of the matrix vessels —(2l)— the biologicalmaterials to be purified are adsorbed to the matrices. It is well knownin the prior art which types of matrices can be used for variousmaterials to be adsorbed. Glass fibre fleeces can for example be usedfor nucleic acids. Reference is made to EP-A-0 738 733 for furtherdetails concerning matrix vessels and the matrices used therein. Thebinding of the biological materials to be isolated to the matrix isprimarily adsorptive i.e. it is based on a physical binding. However,the invention also encompasses those binding processes in which an ionicor covalent bond is formed between the biological materials to beisolated and the matrix material.

After the lysis liquid has been centrifuged through the matrices, thematrices can be washed by adding washing liquid (for example distilledwater) and centrifuging again. Such washing processes can be repeatedseveral times as required. The system composed of matrix unit and wasteunit does not have to be removed from the centrifuge for this; on thecontrary washing liquid can be added directly to the matrix vesselswhile the centrifuge is at standstill.

After the lysis liquids and optionally subsequent washing liquids havebeen removed from the matrix vessels, the matrix unit (20) is removedfrom the waste unit (30) and placed on a collecting unit (40). Thecollecting unit (40) has a number of collecting vessels (41) whichcorresponds to the number of matrix vessels. The matrix unit andcollecting unit are designed such that at least the outlet openings ofthe matrix vessels extend into the collecting vessels when the matrixunit is placed on the collecting unit. Elution fluids are added to thematrix vessels in order to detach the biological substances to beisolated and are pressed through the matrices into the collectingvessels which is preferably carried out by centrifuging the arrangementof matrix unit and collecting unit. Suitable elution fluids for theelution are matched to the materials to be eluted and the matrixmaterial. Elution fluids are well known in the prior art and referenceis made for example to EP-A-738 733.

After the elution purified biological materials are present in thecollecting vessels of the collecting unit (40) which can be used forfurther steps such as the polymerase chain reaction. In a particularlyadvantageous embodiment of the process according to the invention thematrix unit (20) is removed after the elution from the collecting unit(40) and the closure unit (50) is placed on the collecting unit (40).The closure unit (50) has a number of connecting tubes which correspondsto the number of collecting vessels and which make a liquid-tight jointwith the collecting vessel when the closure unit is put on. The top ofthe connecting tubes is closed by caps. In this manner the collectingunit with open vessels can be completely closed in one handling step. Aparticular advantage of this type of closure is that the individualcollecting vessels can be opened individually and thus contaminationscan be completely avoided if the work is carried out carefully.

FIG. 2 additionally shows a coordination unit (60) with a bar codereader (BR) and a computing and storage unit (CPU). According to thepresent invention a process for isolating purified biological materialscan be advantageously carried out by firstly storing the data for asample. This can for example be achieved by reading a bar code on thesample or also by manually entering the data into the storage andcomputing unit. In such a process a code is attached to the lysis unitwhich identifies the entire unit. When a sample is added to a lysisvessel of the lysis unit, the position of the sample within the lysisunit and the code of the lysis unit is entered into the computing andstorage unit. The latter can for example be achieved by reading the codewith a bar code reader (BR). When the lysis liquid from the lysis unit(10) is transferred into the matrix unit (20) the coordination unitregisters from which lysis unit and into which matrix unit the transfertakes place. For this purpose the coding of the matrix unit is assignedto the code for the lysis unit within the coding unit. Furthermore theliquid transfer takes place in a coordinated manner i.e. liquid istransferred from one vessel of the lysis unit (10) into thecorresponding vessel of the matrix unit. The corresponding vessels inthe lysis and matrix unit can be recognized by the user on the basis ofthe position of the vessel within the unit. The units are preferablyadditionally provided with numbers, letters, colours or the like whichallow the user to identify corresponding vessels.

There may also be a code on the collecting unit (40) which is allocatedto the code of the matrix unit. However, a code on the closure unit ispreferably used in order to monitor the position of the samples. Theindividual allocation steps enable an unequivocal allocation of anelution fluid to the sample from which it has been eluted by means ofthe code on the collecting unit or the code on the closure unit (50) andthe position within the collecting unit. The described coding conceptwhich is based on a constant geometric arrangement of the vessels in theindividual units, the codes on the individual units and a coordinatedtransfer of the liquids thus enables a simple and reliable allocation ofthe elution fluids to the original samples. The described conceptachieves a high degree of security against mistakes with little work forthe user. Within the scope of the present invention a geometricarrangement is understood as an arrangement in which several vessels ofa unit are arranged at a regular distance to one another. This is inparticular understood as linear arrangements or arrangements of thevessels in a rectangular shape. Such arrangements enable a systematicprocessing by the user and thus ensure a rapid and reliable operation.

The process of the present invention can additionally be advantageouslycarried out with hinged caps on the lysis unit, matrix unit and/orclosure unit which can take up the following three positions:

An opened position in which liquid is added and removed,

a position in which the cap is lowered and rests on the opening of thevessel below,

a closed position in which the cap's vessel is closed and from which thecap can only be moved into the open position by force or after releasinga fastener.

A process according to the invention can be carried out with such capsin which the caps are in the lowered position before adding liquid, thenthe respective cap of the vessel where an addition is to be made isopened and the cap is completely closed after the addition. In thisprocedure the difference between lowered and completely closed capsenables the user to identify in which vessels an addition has alreadytaken place and which still have to be processed.

The present invention additionally concerns a system for providingbiological materials comprising

a) a collecting unit for collecting the biological material which hastwo or several collecting vessels each of which has an opening which isaccessible from above,

b) a matrix unit with a holder in which the matrix vessels are locatedwhich have an inlet opening for adding a fluid as well as an outletopening for discharging fluid and the matrix vessels are arranged suchthat at least their outlet openings extend into the collecting vesselswhen the matrix unit is placed on the collecting unit,

c) a closure unit which is placed on the collecting unit and which has anumber of connecting tubes which corresponds to the number of collectingvessels and these tubes have a connecting opening and a dischargeopening closed with a cap and connecting tubes with their connectingopenings are attached to the collecting vessels in a water-tight mannerwhen the closure unit is placed on the collecting unit.

The said system facilitates the operations that have to be carried outby the user when providing biological materials by the use of thecollecting unit, matrix unit and closure unit. In particular the systemdiffers from the prior art in that a separate closure unit is used whichis placed on the collecting unit to seal the collecting vessels. Whereasindividual vessels are used in the prior art (see e.g. FIG. 1) whichhave to be individually manipulated by the user, the present systemfacilitates the operating steps of the user by arrangements which haveseveral processing vessels of the same type in a predetermined geometricarrangement. A particular advantage of the system according to theinvention is that the collecting unit with its opened collecting vesselscan be closed in one handling step. FIG. 6 clearly shows that thecollecting unit according to the invention has no cover and thus can beeasily placed under the matrix unit (20). However, assembly of thecollecting vessels shown in FIG. 1 to form a unit of several collectingvessels does not lead to the collecting unit of the present invention.The use of a separate closure unit with connecting tubes which areconnected to collecting vessels is not described in the prior art.

The system according to the invention can additionally include a lysisunit, a waste unit and/or a coordination unit.

The aforementioned units of the system according to the invention aredescribed in more detail with reference to FIGS. 3 to 9.

FIG. 3a shows a lysis unit in a perspective view. The lysis unit (10)shown has two rows of eight lysis vessels (11) each of which are closedby caps (12). The whole lysis unit can be manufactured as a connectedmoulded article in an injection moulding process. Hence suitablematerials for the lysis unit are for example plastics which can beprocessed in an injection moulding process such as polyethylene andpolypropylene. The wall thickness of the lysis unit can be adapted tothe required boundary conditions such as adequate rigidity and heatconduction. Wall thicknesses between 0.5 and 1.5 mm have givensatisfactory results in practice.

FIG. 3a also shows a removable rail (13) which is pushed over the endsof the caps and joins one row of caps together. This rail enables theconnected caps to be simultaneously opened and closed. However, withoutthe rail (13) the caps (12) can be operated completely independently ofone another to enable an independent processing of the lysis vessels. Itis of particular advantage when the other lysis vessels are closed bythe caps when liquids are added or removed. It is advantageous to usecaps (12) which have three positions. In the first position the cap isopen to allow addition and removal of liquids from the lysis vessel. Thecap is lowered onto the lysis vessel in a second position so that thevessel contents cannot be contaminated by dripping liquid or such. Thecap is completely closed in a third position for which the cap is eithermoved over a barrier or closed by a catch.

FIG. 3a additionally shows a tapered pin (14) which extends downwardsfrom the plate (15). The tapered pin is located on one side of the lysisunit which makes it asymmetric. Interaction of the tapered pin (14) witha corresponding recess in a holder unit or such enables a well-definedpositioning of the lysis unit relative to a holder unit or such.

Recesses (16, 16A) are located on the sides of the plate (15) which canalso be used to position the lysis unit.

FIG. 3b also shows that standing elements “(16)” —(17)— are connected tothe plate (15) which are preferably long enough to extend below thebottoms of the vessels. The standing elements enable the lysis unit tobe placed on a flat surface.

FIG. 3b also shows that standing elements (16) are connected to theplate (15) which are preferably long enough to extend below the bottomsof the vessels. The standing elements enable the lysis unit to be placedon a flat surface.

A matrix unit is shown in FIG. 4a which has two rows of eight matrixvessels (21). The matrix vessels (21) can preferably be removed from thematrix unit (20) so that they can be manufactured separately. Each ofthe matrix vessels is allocated a cap (22) which can be used to closethe upper opening of the matrix vessel (application opening). The matrixunit preferably additional has a tapered pin (23) which extendsdownwards from the plate (24). In addition there are recesses (25, 25 a)in the plate (24). The tapered pin and recesses are used to position thematrix unit relative to the collecting unit when the matrix unit isplaced on this unit.

FIG. 4b is a cross-section through FIG. 4a along the line B-B′.Furthermore FIG. 4b shows an arrangement in which the matrix unit isarranged above the waste unit (30). The waste unit (30) which is shownin more detail in FIG. 5, has an individual chamber for each matrixvessel into which the matrix vessel extends. Liquid which emerges fromthe matrix vessel through the lower opening (outlet opening) thus passesdirectly into the corresponding chamber of the waste unit. The relativepositioning of matrix unit and waste unit is achieved by positioningelements. This positioning can be advantageously achieved by the matrixunit enclosing the waste unit with its standing elements as is forexample the case with the lid of a box.

The matrix vessels in the embodiment shown in FIG. 4 are hung in holes.These holes are located in holders (26) that rise up from the plate(24). There is an expansion of the matrix vessels (21) in the region ofthe application opening which rests on the rim of the holder (26).

Matrix vessels which are suitable for use in the present invention havea material in the region of their outlet openings which can specificallybind the biological materials to be isolated. The materials arepreferably porous so that liquid which emerges from the matrix vessel(21) can flow through them. Suitable materials are described in EP-A-0738 733. In addition suitable constructions of matrix vessels arementioned in the said European Patent Application.

FIG. 5 shows a perspective view of a waste unit. The waste unit (30) hastwo rows of eight cavities (31) to receive waste liquids. The cavities(31) are separated from one another by partitions (32) so that the wasteliquids cannot mix. The waste unit additionally has the tubes (33) intowhich the tapered pin (23) of the matrix unit (20) is inserted. Sincethe waste liquids are discarded, the relative orientation of the matrixunit and waste unit is unimportant so that two tubes (33) are providedto simplify the handling for the user. The waste unit can additionallyhave tongues (34) which engage in the slots (25, 25 a) of the matrixunit when it is mounted on the waste unit.

FIG. 6 shows a perspective view of a collecting unit. The collectingunit (40) has two rows of eight collecting vessels (41). The collectingunit is preferably designed as one piece i.e. the collecting vessels(41) and the holder (42) form an integral unit. In order tounequivocally position the matrix unit on the collecting unit, thecollecting unit has a hole (43) into which the tapered pin (23) of thematrix unit engages when the matrix unit is placed on the collectingunit. The interaction between the tapered pin (23) and hole (43)achieves an unequivocal allocation of the matrix vessels to thecollecting vessels. The collecting unit additionally has standingelements (44) to place it on a surface and tongues (45) which engage inthe slots (25, 25 a) of the matrix unit.

The interaction between the matrix unit and collecting unit is shown ingreater detail in FIG. 7. FIG. 7 shows a cross-section through anarrangement of matrix unit and collecting unit. The matrix unit (20)with the matrix vessels (21) which hang in it is arranged on thecollecting unit in such a way that the matrix vessels (21) extend intothe collecting vessels (41). When biological materials are eluted fromthe matrices, the elution fluid thus passes directly into the collectingvessels (41).

After the elution is completed, the matrix unit is removed from thecollecting unit and the collecting unit can be closed with the closureunit shown in FIG. 8a. The closure unit —(50)— has a holder (51) inwhich two rows of eight tubes —(52)— are located. The tubes —(52)— havea part —(55)— which protrudes above the holder —(51) and has a dischargeopening (57)— as well as a pat —(56)— which extends below the holder—(51) and has a connecting opening (59)—. The upper parts —(55)— of thetubes (52)— and thus the discharge openings (57)— are closed by caps(53). The closure unit —(50)— also has a tapered pin (54) which ensuresan unequivocal orientation of the closure unit —(50)— relative to thecollecting unit —(40)—.

An arrangement of closure unit (SO) and collecting unit (40) is shown inFIG. 8b. This figure shows that the parts —(56)— of the connecting tubes—(52)— which extend downwards fit into the collecting vessels. For thispurpose the lower ends of the connecting tubes —(52)— are preferablybevelled to facilitate the fitting in the openings of the collectingvessels. When the closure unit —(50)— is arranged on the collecting unit—(40)—, the connecting tubes —(52)— make a liquid-tight fit in thecollecting vessels. This can be achieved either by a shape fit or apress fit between the collecting vessel and connecting tube. In additionto the embodiment shown in FIG. 8 in which the connecting tube —(52)—engages in the collecting vessel, an embodiment is also possible inwhich the connecting tube embraces the outer contour of the collectingvessel.

FIG. 8 shows connecting tubes with a circular cross-section. However,other cross-sections which differ from this such as ovals, rectanglesand such like are also possible. However, the cross-section of thecollecting vessels and connecting tubes are always matched to achieve aliquid-tight connection when the connecting unit is placed on thecollecting unit.

A type of closure is shown in FIG. 9 that can be used advantageously forthe lysis unit, matrix unit and closure unit. The cap shown isparticularly suitable for the conditions that occur when providingbiological materials. The closure arrangement has a cap (71) which isattached via a hinge (72) (preferably a film hinge) to a vessel orholder. There is a bulge (74) on the cap plate (73) which is used toclose an opening. The bulge preferably has the shape of a truncated coneor spherical segment. A hook plate (75) is attached to the cap plate(73) via one or several hinges (78) (preferably film hinges). There is ahook (76) on this hook plate which can be hooked in a ring. To improvethe handling, the hook plate (75) has a handling tongue (77). As aresult of the described hinges (72 and 78) the closure arrangement hastwo parts which can be moved relative to a vessel or a holder. Inaddition the closure arrangement has a flexible part (79) which isattached to the cap plate (73) and a holder region (80). When the cap isswung from the opened position shown in FIG. 9a into a closed position,the cap passes a position in which the flexible part is stretched and atleast partially relaxes again when it is swung further. The extension ofthe flexible part which is at a maximum at a dead point causes the capto either swing into an opened position or into a position in which itsbulge (74) rests on the rim (81). In this position the opening is notyet closed liquid-tight, but the risk of contamination is greatlyreduced. The cap can be opened again without a large exertion of forcefrom the position in which the cap rests on the opening or the closurearrangement can be completely closed. In order to completely close thecap, the hook (76) can be hooked into a ring (82) by swinging the hookplate (75). Instead of the ring, the vessel can also have a lug underwhich the hook is hooked.

In the hooked position there is a pull on the cap plate (73) whichpresses the bulge (74) into the opening of the vessel and thus seals itgas and liquid-tight. If a liquid is heated in the vessel while the capis clasped, the internal pressure in the vessel increases. However, thecatch efficiently prevents the cap from springing open as a result ofthe interior pressure. This property of the described closurearrangement is particularly important for the lysis of sample liquids inwhich heating is carried out. In addition the closure arrangement can beused for vessels for thermocycling in which an elevated temperature isalso used.

The volume of the cavities of the waste unit is preferably large enoughthat the washing liquids can be collected in addition to the lysismixture without the liquid level touching the outlet opening of thematrix vessels.

If the bulge (74) has the shape of a truncated cone or of a sphericalsegment and the bulge is made of a flexible material, then an increaseof the interior pressure of the vessel deforms the bulge such that theseal between the bulge and vessel rim is increased.

The hooked closure is opened by tilting the hook plate (75) against thecap plate (73). The design of the cap with two plates that can be swungin opposite directions provides a closure arrangement which can beclosed and opened in a simple manner and with little effort and whichensures the sealing of a vessel even with an increased interiorpressure.

List of reference numerals

(1) sample

(2) pipette

(10) lysis unit

(11) lysis vessel

(12) cap of the lysis unit

(13) rail

(14) tapered pin

(15) plate

(20) matrix unit

(21) matrix vessel

(22) cap of the matrix unit

(23) tapered pin

(24) plate

(25, 25 a) slot

(26) holder

(30) waste unit

(31) cavity

(32) partition

(33) tube

(34) tongue

(40) collecting unit

(41) collecting vessel

(42) holder

(43) hole

(44) standing element

(45) tongue

(50) closure unit

(51) holder

(52) connecting tube

(53) cap of the closure unit

(54) tapered pin

(60) coordination unit

(70) closure arrangement

(71) cap

(72) hinge

(73) cap plate

(74) bulge

(75) hook plate

(76) hook

(77) handling tongue

(78) hinge

(79) flexible part

(80) holding region

(81) rim

(82) ring

What is claimed is:
 1. System for providing biological materialscomprising a) a collecting unit for collecting the biological materialwhich has a holder supporting a plurality of collecting vessels each ofwhich has an opening which is accessible from above, b) a matrix unitwith a holder in which matrix vessels are located which have an inletopening for adding a fluid as well as an outlet opening for dischargingfluid and the matrix vessels are arranged such that at least theiroutlet openings extend into the collecting vessels when the matrix unitis placed on the collecting unit, c) a closure unit which is placed onthe collecting unit when the matrix unit is removed from the collectingunit, the closure unit having a closure holder in which connecting tubeswhich corresponds to the number of collecting vessels are located andthe connecting tubes each having a connecting opening and a dischargeopening, the discharge opening being closed with a fit cap and theconnecting tubes with their connecting openings are attached to thecollecting vessels in a water-tight manner when the closure unit isplaced on the collecting unit.
 2. System as claimed in claim 1 with arail which couples two or more first caps together so that the coupledfirst caps can be opened in one operating step.
 3. System as claimed inclaim 1, which additionally includes a lysis unit having lysis vessels,wherein the fluid added to the inlet opening of the matrix vessels istransferred from the lysis vessels.
 4. System as, claimed in claim 3,which additionally includes a coordination unit formed to register fromwhich and into which the lysis unit the matrix unit a transfer of lysisliquid takes place.
 5. System as claimed in claim 1, which additionallyincludes a waste unit on which the matrix unit is placed the matrix unitis removed from the waste unit before being placed on the collectingunit.
 6. System as claimed in claim 1, wherein the matrix vesselsarranged in the holder can be removed.
 7. System as claimed in claim 1,wherein second caps whose number corresponds to the number of matrixvessels are attached to the matrix unit and are used to close the inletopenings of the matrix vessels.
 8. System as claimed in claim 7, whereintwo or more of the second caps are connected by a rail so that theconnected caps can be opened or closed together in one handling step. 9.System for providing biological materials comprising a collecting unithaving a holder supporting collecting vessels, each vessel having anopening, a matrix unit having a plate with holder and matrix vessels,each vessel resting upon one of the holders and having an inlet openingfor adding a fluid as well as an outlet opening for discharging fluidand the matrix vessels being arranged such that at least the outletopenings extend into the collecting vessels when the matrix unit isplaced on the collecting unit, and a closure unit formed to be placed onthe collecting unit when the matrix unit is removed from the collectingunit, the closure unit having a closure holder in which connecting tubesare located, the connecting tubes being attached to the collectingvessels in a water-tight manner when the closure holder of the closureunit is placed on the holder of the collecting unit, the connectingtubes each having a connecting opening and a discharge opening, thedischarge opening being closed with a first cap.
 10. System as claimedin claim 9 wherein the closure unit includes a rail that couples two ormore first caps together.
 11. System as claimed in claim 9 furthercomprising a lysis unit that is spaced-apart from the matrix unit. 12.System as claimed in claim 11 further comprising a coordination unitformed to register from which lysis unit and into which matrix unit atransfer of lysis liquid takes place.
 13. System as claimed in claim 9further comprising a waste unit, the matrix unit being selectivelyplaced on the waste unit.
 14. System as claimed in claim 9 wherein thematrix vessels are removable from the matrix unit.
 15. System as claimedin claim 9 wherein the matrix unit includes second caps whose numbercorresponds to the number of matrix vessels.
 16. System as claimed inclaim 15 wherein two or more of the second caps of the matrix unit areconnected by a rail.
 17. System for providing biological materialscomprising a collecting unit having a collecting holder supportingcollecting vessels, each vessel having an opening, a matrix unit havinga plate, holders extending from the plate and defining holes, and matrixvessels, each vessel extending through one of the holes and resting uponone of the holders, each vessel having an inlet opening for adding afluid as well as an outlet opening for discharging fluid and the matrixvessels being arranged such that at least the outlet openings extendinto the collecting vessels when the matrix unit is placed on thecollecting unit, and a closure unit formed to be placed on thecollecting unit when the matrix unit is removed from the collectingunit, the closure unit having a closure holder containing connectingtubes attached to the collecting vessels in a water-tight manner whenthe closure unit is placed on the collecting unit, the connecting tubeshaving a connecting opening and a discharge opening, the dischargeopening being closed with a first cap.
 18. System as claimed in claim 17wherein the closure unit includes a rail that couples two or more firstcaps together.
 19. System as claimed in claim 17 further comprising alysis unit that is spaced-apart from the matrix unit.
 20. System asclaimed in claim 19 further comprising a coordination unit formed toregister from which lysis unit and into which matrix unit a transfer oflysis liquid takes place.
 21. System as claimed in claim 17 furthercomprising a waste unit, the matrix unit being selectively placed on thewaste unit.
 22. System as claimed in claim 17 wherein the matrix vesselsare removable from the matrix unit.
 23. System as claimed in claim 17wherein the matrix unit includes second caps whose number corresponds tothe number of matrix vessels.
 24. System as claimed in claim 23 whereintwo or more of the second caps of the matrix unit are connected by arail.